Project Summary: The long-term objective of this application is to develop a career as an independent researcher focusing on the genetic and environmental etiology of depression, anxiety disorders, and posttraumatic stress disorder (PTSO). A better understanding of the genesis of these disorders would help develop more targeted prevention and treatment strategies. This objective is consistent with the National Institute of Mental Health's mission to reduce the burden of mental disorders. The career development award will build on the investigator's strong background in psychiatric epidemiology and applied statistics to develop expertise in genetic epidemiology and applied statistical genetics. The specific aims of the proposed research study are to conduct a genetic linkage study of depression and anxiety disorders to identify genes that influence their development in an Arab Bedouin kindred in a village in Northern Israel. This kindred has high rates of suicide, depression, and anxiety disorders (12 percent, 30 percent, and 36 percent, respectively). This kindred is also highly homogeneous originating from one founder and has high rates of endogamy, which make it unique and promising for identifying genes influencing these phenotypes. We will also conduct linkage analysis of neuroticism, a personality trait referring to emotional reactivity, as a quantitative endophenotype that may represent an intermediate form of expression between genes and phenotypes. As an exploratory aim, we will conduct linkage analyses of PTSD and examine the interaction between genes and stressful life events in their influence on depression and PTSD. Relevance: Almost 50 percent of the population in the United States suffer from at least one mental health disorder. Depression and anxiety disorders are the most common and thus constitute a major public health problem. The proposed study will allow us to identify genes associated with depression and anxiety disorders and would greatly advance our ability to identify subjects at high risk and develop treatment for these disorders.